| Summary: | 碩士 === 國防醫學院 === 生物及解剖學研究所 === 102 === MDMA is a synthetic stimulant in the central nervous system, commonly known as ecstasy. It is now a popular choice of abused drug among adolescents and young adults in the nightclubs. Researches show that sustained high doses of MDMA may induce neurotoxicity in the serotonin system. In this study, we evaluated the neuroprotective effect of amitriptyline, paroxetine, and 3-methyladenine against MDMA toxicity using non-invasive micro-SPECT coupled with [123I]ADAM (a serotonin transporter imaging agent). Previous literature shows that these drugs might exert neuroprotective effects either by blocking serotonin transporter or inhibiting cell autophagy. However, the effects of these drugs on the MDMA-induced serotonergic neurotoxicity remain to be elucidated. The results of this study showed that one week after MDMA-treatment caused 42% reduction of specific uptake ratios (SURs) of [123I]ADAM compared to those of normal group. In the MDMA/paroxetine and MDMA/amitriptyline、MDMA/3MA co-treated groups, the uptakes of [123I]ADAM in the midbrain, thalamus, striatum, and frontal cortex showed higher SURs than those of MDMA group. (MDMA-3MA was 51%, MDMA-TCA was 51% and MDMA-Paroxetine was 41.2% higher than those of MDMA group). In the fourth week after the drugs treatment, the results also showed the similar trend. Furthermore, the immunohistochemical staining results of serotonin transporter and the results of micro-SPECT are consistent. These results indicate that micro-SPECT coupled with [123I]ADAM could be a preclinical screening platform to evaluate the drugs against MDMA-induced neurotoxicity.
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